Design, Synthesis, and Anti-mycobacterial Evaluation of New 3,5-Disubstituted-pyrazole-1-carbothioamides

Kok Tong Wong; Hasnah Osman; Thaigarajan Parumasivam; Muhammad Solehin Abd Ghani; Mohd. Zaheen Hassan; Unang Supratman; Mohamad Nurul Azmi Mohamad Taib

doi:10.22146/ijc.70243

Design, Synthesis, and Anti-mycobacterial Evaluation of New 3,5-Disubstituted-pyrazole-1-carbothioamides

https://doi.org/10.22146/ijc.70243

Kok Tong Wong⁽¹⁾, Hasnah Osman⁽²⁾, Thaigarajan Parumasivam⁽³⁾, Muhammad Solehin Abd Ghani⁽⁴⁾, Mohd. Zaheen Hassan⁽⁵⁾, Unang Supratman⁽⁶⁾, Mohamad Nurul Azmi Mohamad Taib^(7*)

(1) School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
(2) School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
(3) School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
(4) School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
(5) School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia; College of Pharmacy, King Khalid University, Abha, Kingdom of Saudi Arabia
(6) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor 45363, Indonesia
(7) School of Chemical Sciences, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia
(*) Corresponding Author

Abstract

Two series of new 3,5-disubstituted-pyrazole-1-carbothioamides (4a-f and 5a-e) were designed and synthesized through condensation reaction between chalcones and thiosemicarbazides under alkaline condition via cyclocondensation reaction. The structures have been elucidated by Fourier-transform infrared (FTIR), High-resolution mass spectrometry (HRMS), one- and two-dimensional nuclear magnetic resonance (NMR) analyses. These compounds were assayed for in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Ra using the Tetrazolium microplate assay (TEMA) method. As a result, six compounds (i.e., 4a, 4d, 4f, 5a, 5c, and 5d) showed a weak activity with minimum inhibition concentration (MIC) between 650–530 μM, and other compounds showed no inhibition against MTB. In addition, all tested compounds also did not show any cidal effects for minimum bactericidal concentration (MBC), even at the highest test concentration.

Keywords

3,5-disubstituted-pyrazole-1-carbothioamide; pyrazolines; Mycobacterium tuberculosis; antitubercular agents; anti-mycobacterial

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DOI: https://doi.org/10.22146/ijc.70243